Therapeutic ID93 + GLA-SE Vaccination in Participants With Rifampicin-Susceptible Pulmonary TB

This study is being done to test an experimental study vaccine compared to a placebo. The experimental study vaccine is called ID93 + GLA-SE. ID93 + GLA-SE has been used in humans in research but has not been approved for use in medical care. This study will be the first to test ID93 + GLA-SE in people living with HIV (PLWH). The injections during the study will be given to different groups of participants while they are using standard TB treatment. One of the research questions is to understand the differences in immune system responses depending on the timing of giving the injections after people begin taking standard TB treatment. Researchers also want to continue to look at whether the study vaccine is safe when tested in a larger group of people, and if getting the study vaccine in addition to standard TB treatment can help to lower the number of poor TB outcomes that people might have.

Inclusion Criteria Groups 1-5: * Bacteriologically confirmed rifampicin-susceptible pulmonary TB using phenotypic drug susceptibility testing or a World Health Organization (WHO) approved molecular test. * Documentation of HIV status as positive or negative by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit. * For individuals with HIV, on locally approved HIV ART for at least 90 days prior to entry. * For individuals with HIV, CD4+ cell count ≥250 cells/mm3 obtained within 90 days prior to entry at any network-approved non-US laboratory that is DAIDS IQA certified. * For individuals with HIV, HIV-1 RNA below the limit of detection obtained within 90 days prior to entry by any network-approved laboratory outside the US that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs. * Laboratory values within the indicated ranges, obtained within 14 days prior to entry by any network-approved laboratory outside the US that operates in accordance with GCLP and participates in appropriate external quality assurance programs. * Absolute neutrophil count (ANC) ≥800 cells/mm3 * Hemoglobin ≥8.5 g/dL for candidates assigned female sex at birth and \>9.0 g/dL for candidates assigned male sex at birth * Platelet count ≥100,000/mm3 * Serum creatinine ≤1.5 X upper limit of normal (ULN) * AST (SGOT), ALT (SGPT), and alkaline phosphatase, ≤2.5 X ULN * Total bilirubin ≤2 X ULN * For candidates who are able to become pregnant, negative serum or urine pregnancy test at or within 7 days prior to entry by any network-approved laboratory or clinic outside the US that operates in accordance with GCLP and participates in appropriate external quality assurance programs. * Candidates who are able to become pregnant must agree to use an adequate method of contraception (barrier methods or non-hormonal intrauterine device) or abstain from sexual activity that could lead to pregnancy from at least 21 days prior to the first scheduled vaccination through 90 days after last dose. * Candidates assigned female sex at birth (AFAB) must agree to not seek pregnancy through alternative methods, such as oocyte retrieval, artificial insemination, or in vitro fertilization, from at least 21 days prior to the first scheduled vaccination through 90 days after last dose. * For candidates who are not of child-bearing potential, acceptable documentation (written documentation or oral communication from a clinician or clinician's staff documented in source documents: physician report/letter, operative report or other source documentation in the candidate record, discharge summary, laboratory report, etc.) of hysterectomy and bilateral oophorectomy, tubal ligation, tubal micro-inserts, vasectomy, or menopause. * Ability and willingness of candidate to provide informed consent. Inclusion Criteria Groups 1 and 2 \[Step 2\]: * Documented duration of local SOC TB treatment prior to entry into Step 2 (study entry) for i. Group 1 of between 113 and 127 days (i.e., approximately 4 months of TB treatment) ii. Group 2 of between 83 and 97 days (i.e., approximately 3 months of TB treatment) Inclusion Criteria, Groups 3, 4, and 5 \[Step 1\]: * Initiation of local SOC TB treatment within 7 days prior to entry into Step 1 (Study entry). Exclusion Criteria Groups 1-5: * Documented M.tb resistance to isoniazid. * Breastfeeding. * Any previous episode of TB treatment. * TB treatment with a local non-standard first-line TB treatment regimen at time of enrollment. * Receipt of any investigational drug or any investigational non-TB vaccine since start of TB treatment. * Any prior receipt of any investigational TB vaccine. * Known allergy or any hypersensitivity to any components of study product or their formulation or any vaccination. * Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. * History of moderate to serious autoimmune disease requiring immunosuppressive therapy. * Receipt of immunosuppressive medications (except as noted below) from start of TB treatment. * Corticosteroid nasal spray * Inhaled corticosteroids * Topical corticosteroids for mild, uncomplicated dermatologic condition * A single course of oral/parenteral prednisone or equivalent at doses \